gastrins and Carcinoma--Islet-Cell

Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

Topics: Adenoma, Islet Cell; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Islet Cell; Catheter Ablation; Chemoembolization, Therapeutic; Evidence-Based Medicine; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Quality of Life; Somatostatin; Survival Analysis; Treatment Outcome

The objective of this study was to investigate spontaneous islet cell carcinomas with particular reference to possible existing strain differences between Sprague Dawley (SD) and Wistar (W) rats in incidence and immunohistochemical staining pattern. Secondly the occurrence of somatostatin and/or gastrin-positive islet cell tumors should be tested. Islet cell adenocarcinomas (34 from SD, 43 from W-rats) were selected from the RITA-data base and company in-house data base out of an animal pool of 3915 (1681 SD, 2234 W-rats). They were untreated or sham-treated (vehicle) control animals from carcinogenicity studies and whole life-span experiments. Islet cell carcinomas occurred in a higher incidence in male rats (2.98% for SD, 3.23% for W) than in female rats (1.07% for SD, 0.63% for W). All specimens were immunohistologically stained with antibodies against insulin, glucagon, somatostatin and gastrin and, selected specimens with additional antibodies (pancreatic polypeptide, lipase, chymotrypsin, S100-protein, actin and cytokeratin). 94% (SD) and 93% (W), respectively, were insulin-positive and the mean staining intensity (on a scale ranging from 0-4) for insulin was 3.58 (SD) versus 3.37 (W). This high insulin staining incidence and intensity characterized most islet cell carcinomas as malignant insulinomas. 24% (SD) and 37% (W), respectively, were glucagon-positive. Except two tumors in W-rats with a focal strong glucagon expression, the mean staining intensity for glucagon was low (0.38 SD, 0.72 W). 38% (SD) and 44% (W), respectively, were somatostatin-positive, but except for five cases having a focal to multifocal, moderate to marked staining, only a few tumor cells were positive for somatostatin in the other cases and the mean staining intensity for somatostatin was low (0.50 SD, 0.84 W). 6% (SD) and 23% (W), respectively, were gastrin-positive, but only one case of a male Wistar rat exhibited a focal strong staining in parts of the tumor. The other cases showed only a few tumor cells which were positive for gastrin. The mean staining intensity for gastrin was low (0.06 SD, 0.35 W). In all tumors with marked glucagon, somatostatin or gastrin expression, the immunostaining for insulin was still predominating. Thus, insulin was the major hormone produced by most of the tumor cells. Five out of 77 tumors evaluated were immunohistologically negative with all applied antibodies.. This study presents the first immunohistochemical survey on spontaneous islet cell carcinomas in SD and Wistar rats stained with antibodies against the endocrine pancreas hormones insulin, glucagon, somatostatin and gastrin. No major differences in incidence or immunohistochemical staining pattern between SD and W-rats could be detected. In contrast to SD rats, Wistar rats had multihormonal coexpression in 16.3%. The multihormonal appearance of the neoplasms is well comparable with the findings in other animal species and human insulinomas. Moreover, this is the first study in rats which reports five cases with a marked co-expression of somatostatin and one case with marked focal co-expression of gastrin in malignant islet cell adenocarcinomas.

Topics: Animals; Antibodies, Neoplasm; Biomarkers, Tumor; Carcinoma, Islet Cell; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Insulin; Male; Pancreatic Neoplasms; Rats; Rats, Sprague-Dawley; Rats, Wistar; Registries; Somatostatin

We report the case of a 49-year-old caucasian woman, in whom an endocrine tumor arising in gastric heterotopic pancreas was diagnosed. The patient was treated surgically with a gastric wedge resection. Heterotopic pancreas is a benign anatomic condition, probably widely underdiagnosed because usually asymptomatic. The malignant transformation of aberrant pancreas is very rare and almost always in adenocarcinoma. The endocrine tumors developed in heterotopic pancreas are exceedingly rare. Of our knowledge, only four cases have been published and only one case in the gastric location similar to this reported case.

Topics: Carcinoma, Islet Cell; Cell Transformation, Neoplastic; Choristoma; Female; Follow-Up Studies; Gastrins; Humans; Islets of Langerhans; Middle Aged; Pancreas; Pancreatic Neoplasms; Somatostatin; Stomach Diseases

Neoplasms of the pancreas usually show ductal, acinar or endocrine differentiation. Tumors with mixed exocrine and endocrine components are unusual. We herein describe a case of a mixed ductal-endocrine tumor.. A 65-year-old woman was referred to our department with a diagnosis of carcinoma of the tail of the pancreas. The patient had a short history of upper abdominal pain, nausea and melena. Upper gastrointestinal endoscopy revealed gastric fundus varices and CT scan demonstrated an inhomogeneous tumor located in the tail of the pancreas infiltrating the spleen and the splenic vein. The patient underwent distal pancreatectomy and splenectomy, and had an uneventful recovery. Pathological examination revealed a mixed ductal-endocrine tumor. The endocrine component was immunoreactive for glucagon, gastrin and somatostatin, and non-reactive for insulin.. Because of the rarity and unpredictable biologic behavior of these tumors, the need for adjuvant therapy has not yet been well-defined. The patient has had a follow-up CT scan every six months, and one and a half years later remains disease free.

Topics: Aged; Carcinoma, Islet Cell; Carcinoma, Pancreatic Ductal; Chromogranins; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Mixed Tumor, Malignant; Pancreatic Neoplasms; Phosphopyruvate Hydratase; Somatostatin

Topics: Adrenocorticotropic Hormone; Carcinoma, Islet Cell; Cushing Syndrome; Diagnosis, Differential; Gastrins; Heartburn; Humans; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Tomography, X-Ray Computed

It is well known that an islet cell tumor can secrete multiple hormones depending on its cell type. We report the case of a 70-year-old woman who initially presented with peptic ulcer symptoms, an elevated serum gastrin level, and multiple liver tumors. Liver biopsy and distal pancreatectomy were performed, and the pathological diagnosis was malignant islet cell tumor. Additionally, the immunohistochemical staining revealed scattered positivity for gastrin, and then also positivity for insulin 14 months later. A subsequent hypoglycemic episode and elevated serum gastrin and insulin levels suggested that the disease had developed into a condition of multiple hormone secretion. The plasma gastrin and insulin levels decreased from 584 pg/ml and 90.8 microIU/ml to 49.1 pg/ml and 20.9 microIU/ml, respectively, 5 days after treatment with subcutaneous octreotide 100 micrograms every 6 to 8 hours. In addition, follow-up computed tomography showed shrinkage of the metastatic liver tumors. In conclusion, we found a case of malignant islet cell tumor with variable hormone secretion which could be effectively controlled with octreotide.

Topics: Aged; Carcinoma, Islet Cell; Female; Gastrins; Humans; Immunohistochemistry; Insulin; Octreotide; Pancreatic Neoplasms

Topics: Carcinoma, Islet Cell; Fatal Outcome; Female; Gastrins; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms

The production of ACTH-like material by tumours arising in non-endocrine tissue may initiate severe adrenocortical hyperfunction. The pathogenesis and clinical and laboratory features of Cushing's syndrome associated with such tumours are characteristic. The autonomous production by the tumour of ACTH-like material cannot be suppressed by exogenous corticoids. The onset of clinical symptoms is rapid; muscle wasting, general weakness, thirst and peripheral edema predominate, and the classical signs of Cushing's syndrome may be absent. High levels of plasma 17-hydroxycorticosteroids and urinary 17-hydroxycorticosteroids and 17-ketosteroids, usually with normal levels of urinary aldosterone, commonly occur. Hypokalemic alkalosis unresponsive to replacement therapy may cause death. In the case reported herein, the intriguing possibility exists that two hormone-like substances were produced by the primary growth and its metastases: one, ACTH-like, to account for the adrenal hyperplasia and Cushing's syndrome; and another, gastrin-like, giving rise to the ulcerogenic diathesis.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma, Islet Cell; Adrenalectomy; Adrenocortical Hyperfunction; Autopsy; Carcinoma, Islet Cell; Chloramphenicol; Cushing Syndrome; Drug Therapy; Gastrins; Humans; Hypokalemia; Neoplasm Metastasis; Neoplasms; Pancreatic Neoplasms; Pathology; Spironolactone; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoma, Islet Cell; Gastrins; Humans; Pancreatic Neoplasms; Peptic Ulcer; Stomach; Zollinger-Ellison Syndrome